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Cullin-RING ligases are regulated by the COP9 signalosome (CSN) through deneddylation. Here, authors report high-resolution cryo-EM structures that capture catalytic and dissociation intermediates, identify CSNAP within the complex, and reveal a stepwise pathway for CSN disengagement.

A skeletal editing strategy for the direct conversion of oxazoles and isoxazoles into thiazoles and isothiazoles is described. These one-step transformations may be beneficial for drug development programmes by enabling rapid diversification of bioactive compounds and advancing structure–activity relationship studies.

A combination of biochemical, cell biological and electron microscopy analyses reveal a ‘nucleotide code’ that coordinates Lis1–dynein binding stoichiometry, which in turn governs Lis1’s ability to relieve dynein autoinhibition.

Spatiotemporal insight into photoactivation of the prototypical B₁₂ photoreceptor CarH is revealed across nine orders of magnitude in time, identifying a transient adduct that distinguishes it from thermally activated B₁₂ enzymes.

The distinct architecture of the Escherichia coli membrane transporter LetA mediates lipid trafficking across the bacterial envelope in partnership with the tunnel-like complex LetB.

On-surface synthesis recently enabled access to generate a series of cyclo[n]carbons via delicately designed precursors but for large cyclocarbons, synthesis of the corresponding precursors is challenging. Here, the authors report a strategy for synthesizing larger cyclocarbons via the coupling and ring-opening reactions from smaller ones.

Pangenomic and epidemiological analyses reveal a genetic shift in U.S. Salmonella Hadar populations during 2019–20, driven by expansion of a lineage carrying a prophage-like element that likely arose in commercial poultry and spread to backyard flocks.

Low oxidation state aluminium complexes have gained wide recognition as discrete and versatile 2-electron reductants, but neutral trimeric structures remain elusive. Here the authors report the synthesis and characterization of two neutral Al(I) trimers whose trimeric structure is retained in solution.

PCNA–PAF15 has a key role in determining replisome dynamics during genome replication and protecting against genome instability.

An amino-acid-encoded assembly strategy is developed for the synthesis of programmable chiral Solomon links, featuring tunable cavity dimensions and shapes. This template-free synthetic approach favours homochiral assembly over non-chiral or heterochiral pathways. The resulting interlocked molecules exhibit strong chiral amplification and exceptional enantioselective peptide recognition.

ALMA has captured exquisitely detailed images of bowshock shells in the outflow of an outbursting protostar. These provide important insights into the variable nature of the ejections from protostars, which play a key role in star and planet formation.

How animals detect external touch while their sensory organs are in constant motion remains unclear. Here, the authors show that specialized receptors in rat whisker follicles are structurally tuned to ignore self-motion and respond only to touch.

DNA replication stress is a driver of genome instability. Here, the authors identify a role of the E3 ligase RNF25 in promoting replication stress tolerance. Mechanistically, RNF25 recruits the fork protection factor REV7 to stalled replication forks and prevents nucleolytic degradation.

Intramolecular coupling of extended biphen[n]arenes is developed to yield cycloparaphenylenes (CPPs). The modular nature of biphen[n]arenes makes it possible to customize CPP structures, which permits tuning of their photophysical properties. The syntheses are short and excellent yields are achieved. Moreover, postsynthetic functionalization is possible.

Natural products populate areas of chemical space not occupied by average synthetic molecules. Here, an analysis of more than 180,000 natural product structures results in a library of 2,000 natural-product-derived fragments, which resemble the properties of the natural products themselves and give access to novel inhibitor chemotypes.

Exploration of the chemistry of allylic, benzylic, propargylic and allenylic oxonium ions is lacking despite the latest developments in onium ion chemistry. Now, a unified approach for the synthesis and NMR spectroscopic characterization of these unusual species is reported, helping to understand their reactivity.

Broadly applicable genetically encoded probes and peptide-based compounds specifically inhibit Gα_s, the prototypical signal transducer of G-protein-coupled receptors, providing new mechanistic insights into signaling at the subcellular scale.

Using a molecular engineering approach, wafer-scale uniaxially oriented Te nanowire thin films are synthesized with excellent controllability and uniformity. The anchor-rope structural molecules form a periodic self-assembled supramolecular membrane, which facilitates the adsorption and well-arranged growth of Te nanowires on grooved sapphire.

Chemical reactions with incompatible mechanisms are usually difficult to perform simultaneously in one-pot. Here the authors report a method where cationic ring-opening polymerization of 2-oxazolines and anionic ring-opening polymerization of cyclic esters can be initiated sequentially and propagate simultaneously in one-pot, using bismuth salts as the initial initiators.

Frontal ring-opening metathesis polymerization (FROMP) is a promising energy-efficient approach to fabricate polymeric materials but the characteristic properties of the front are currently controlled primarily by varying the resin composition or the environmental conditions. Here, the authors present an approach to control FROMP of dicyclopentadiene using photochemical methods.

Despite the frequent presence of para-cyclophane scaffolds in natural products and bioactive molecules, their synthesis remains challenging. Now a series of para-cyclophanes bearing bent 1,4-disubstituted benzene subunits with a high degree of distortion are readily prepared between cyclic tertiary amines and aryne intermediates via a N-arylation–ring-expansion [5,5]-sigmatropic rearrangement process.

The structural anisotropy necessary for the powered directional rotation of chemically fuelled molecular motors had previously been provided by chiral fuels or enzymes. Now it has been shown that asymmetry in the organocatalyst itself is sufficient for directional fuelled rotation. This informs how chemical energy is transduced through catalysis, the fundamental process that powers biology.

Quantum technology concepts rely on efficient control of the system state, such as the electron spin. Here the authors present a mechanism for spin and orbital manipulation based on hybridizing quantum dot states at two points inside InAs nanowires, resulting in tunable quantum rings with giant controllable g-factors.

The substantia nigra and all Parkinson’s disease deep-brain stimulation targets are selectively connected to the somato-cognitive action network rather than to effector-specific motor regions.

Compound MMV006833 inhibits ring-stage development of Plasmodium falciparum. Here, the authors show that it targets lipid transfer enzyme PfSTART1 and prevents PfSTART1 from expanding the vacuole membrane encasing the parasite after red blood cell invasion, thereby blocking parasite growth.

Schizogony is essential for blood stage infection of Plasmodium parasites and produces several daughter cells. Here, Rudlaff et al. identify PfCINCH and interacting proteins as essential components of the basal complex required to establish daughter cell boundaries.

Using chemical photoswitchable reagents to exert purely wavelength-dependent control over biological systems in deep tissue and in vivo requires a concentration-independent design paradigm. Here, such photoswitchable ligands are realized by ensuring that E/Z isomers have opposing efficacies yet similarly high affinity, allowing them to probe transient receptor potential C4 and C5 channel functions up to the tissue level.

The authors report observations of a dense and inhomogeneous ring at a surprisingly large distance from the trans-Neptunian body Quaoar.

Space missions imaging small asteroid moons revealed the variety in shapes. Here, the authors show that repeated low-speed collisions can explain the shape of Selam, which is the smaller component in Dinkinesh-Selam binary asteroid system.

Spatially resolved images of M87 obtained at a wavelength of 3.5 mm in 2018 show a ring-like accretion structure, the inner (outer) edge of which connects the black hole (jet).

Benzene formation via sequential cold ion–molecule reactions is followed experimentally to understand how aromatic molecules are formed in interstellar clouds. Surprisingly, the chain of reactions involving the addition of acetylene terminates at C₆H₅⁺.

In this work, a library of several hundred million compounds was computationally docked to a cryoEM structure of the orphan G protein-coupled receptor GPR139, leading to the discovery of a potent agonist with in vivo effects and insights into GPR139 signalling.

The tumour microenvironment in signet ring cell carcinoma (SRCC) remains to be characterised. Here, the authors perform single-cell RNA sequencing and reveal distinct features compared to moderately/poorly differentiated adenocarcinoma.

The authors theoretically delineate the maximal increases in tree growth that can be expected from increases in plant intrinsic water-use efficiency, which increases with rising CO₂. They highlight environmental and physiological limits on growth in the context of experimental data.

An extreme Einstein ring ~10,000 times as bright as the Milky Way in the infrared is studied with VLT/ERIS and ALMA, and the authors find that the lensed galaxy is a starburst with a fast-rotating disk, rather than being driven by a major merger.

Break-induced replication (BIR) repairs broken DNA but can also destabilize genomes. The authors identify 33 new genes controlling BIR completion, showing that spindle assembly and spindle positioning checkpoints coordinate repair, and that nuclear pore proteins regulate BIR at multiple steps.

Pseudaminic acids (Pse) are a family of carbohydrates found within bacterial lipopolysaccharides, capsular polysaccharides and glycoproteins. Now, monoclonal antibodies have been developed that recognize diverse Pse across several bacterial species, enabling mapping of the Pse glycoproteome and demonstrating therapeutic potential against multidrug-resistant Acinetobacter baumanii in in vitro and in vivo infection models.

Tree longevity is thought to increase in harsh environments, but global evidence of drivers is lacking. Here, the authors find two different pathways for tree longevity: slow growth in resource limited environments and increasing tree stature and/or slow growth in competitive environments.

The nuclear clock transition of ^229mTh in ²²⁹Th:CaF₂ crystals is characterized as a function of doping concentration, temperature and time, demonstrating high reproducibility and identifying ideal operating characteristics of these crystals as nuclear clocks.